The proposed research project is a longitudinal epidemiologic study aimed at confirming or refuting the hypothesis that long-term low selenium exposure is associated with greater cognitive decline. Selenium is a trace element associated with the activity of the antioxidant enzyme glutathione peroxidase. It is considered to be a defensive agent against free radicals through the maintenance of better enzyme activity. Associations between low selenium and increased risk in various disease indices (cancer, cardiovascular disease, reproduction and neonatal health, and asthma) have been reported. The limited studies on selenium and cognitive function or Alzheimer's disease, however, have not reached unequivocal conclusions. Studying the relationship between long-term selenium exposure and cognitive decline in the US population is difficult because the population is mobile and consumes foods that were produced and prepared in different areas of the world. Selenium exposure in the US population is also highly confounded by supplements that are related to the socio-economic and health status of the individuals. The rural Chinese population, in contrast to the US population, is unusually stable with most living in the same village throughout their entire life and consuming food that is locally grown. It is also rare for these villagers to take dietary supplements. Most importantly, selenium as an environmental agent has been studied extensively by Chinese scientists. We propose to conduct a longitudinal study on approximately 2000 rural Chinese age 65 and over with half of them from low selenium areas and the other half from normal selenium areas. The stability of this rural population allows for lifetime exposure estimates to environmental selenium. We hope to test the hypothesis that low selenium exposure is associated with greater cognitive decline. We will also determine the APOE genotype distribution in this population and test the hypothesis that possessing an APOE e4 increases the risk for cognitive decline. We will investigate whether the strength of the association between low selenium and cognitive decline is affected by APOE genotype. In addition we will try to identify other risk factors associated with cognitive decline in this population.